title: TOP2A protein by quantitative immunofluorescence as a predictor of response to epirubicin in the neoadjuvant treatment of breast cancer.
abstract: OBJECTIVE
  Anthracyclines are commonly used in breast cancer, although they lack validated predictive biomarkers. We explored the interaction between TOP2A protein by quantitative immunofluorescence (QIF) and anthracycline sensitivity.
  
  
  METHODS
  Patients with estrogen receptor-negative breast cancer received neoadjuvant epirubicin. Pretreatment biopsies were analyzed using AQUA(®). Total, cytoplasmic (C) and nuclear (N) TOP2A protein concentrations were expressed as QIF scores and compared with pathologic complete response (pCR), TOP2A by immunohistochemistry, TOP2A mRNA, TOP2A and HER2 gene status, and Ki-67 level.
  
  
  RESULTS
  In total, 76 cases were assessable. C, N, and total scores did not correlate with pCR, or other markers. The N:C ratio differed significantly by HER2 status. No pCRs occurred in patients in the lowest N:C quartile.
  
  
  CONCLUSIONS
  Although no relevant correlation between TOP2A QIF scores and pCR was found, N:C ratio may have a negative predictive role, and may merit further exploration in a multifactorial predictive model that includes tumor and host factors.
authors.affiliation: 'Sandro Pitigliani' Medical Oncology Unit, Hospital of Prato, Istituto Toscano Tumori, Piazza Ospedale 2, 59100, Prato, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Moretti
authors.forename: Christine
authors.initials: C
authors.lastname: Desmedt
authors.forename: Chiara
authors.initials: C
authors.lastname: Biagioni
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Regan
authors.forename: Catherine
authors.initials: C
authors.lastname: Oakman
authors.forename: Denis
authors.initials: D
authors.lastname: Larsimont
authors.forename: Francesca
authors.initials: F
authors.lastname: Galardi
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart-Gebhart
authors.forename: Christos
authors.initials: C
authors.lastname: Sotiriou
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
authors.forename: Angelo
authors.initials: A
authors.lastname: Di Leo
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015251:Epirubicin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020360:Neoadjuvant Therapy; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D021381:Protein Transport; D059005:Topoisomerase II Inhibitors / Q000627:therapeutic use*
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D059005:Topoisomerase II Inhibitors; D015251:Epirubicin; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human